tbuckley/cabot-search huggingface dataset:
Whole exome sequencing and machine learning germline analysis of individuals presenting with phenotypes of extreme high and low risk of developing tobacco-induced lung adenocarcinoma.
Authors: Jose Luis Perez-Gracia, Elisabet Guruceaga, Maria Pilar Andueza, Marimar Ocon, Nicolas de VIllalonga Zornoza, Jafait Junior Fodop Sokoudjou, Gorka Alkorta-Aranburu, Carlos Camps, Eloisa Jantus-Lewintre, Maria Navamuel Andueza, Miguel F. Sanmamed, Alfonso Gurpide, Ignacio Melero Bermejo, Mohamed Elgendy, Juan Alberto Perez Valencia, Mikel Hernaez, Ruben Pio Oses, Luis M. Montuenga, Idoia Ochoa, Ana Patiño-García
Journal: Journal of Clinical Oncology (2023)

10507 Background: Tobacco is the main risk factor for developing lung cancer. Yet, while some heavy smokers develop lung cancer at young age others never develop it, even at advanced age. This suggests a remarkable variability in the individual susceptibility to the carcinogenic effects of tobacco. We characterized the germline profile of subjects presenting these extreme phenotypes with Whole Exome Sequencing (WES) and Machine Learning (ML). Methods: We sequenced germline DNA from heavy smokers who either developed lung adenocarcinoma at early age ( extreme cases) or did not develop it at advanced age ( extreme controls). The discovery and validation cohorts included respectively 50 and 66 extreme cases and 50 and 83 extreme controls, selected from databases including &gt; 6,000 subjects. We selected individual coding variants and variant-rich genes showing a significantly different distribution between extreme cases and controls. We trained ML models (Logistic Regression, Random Forest, Support Vector machine Classifier (SVC)) on the discovery cohort to classify subjects into their respective phenotypes and tested them on the validation cohort. Results: Mean age for extreme cases and controls in both cohorts was 50.2 and 78.4 years. Mean tobacco consumption was 38.1 and 59.1 pack-years. We validated 16 significant individual variants. The most significant variants were in ADAMTS7 (2 variants) in cases and TMEM191B (1) in controls. We validated 33 genes enriched with significant variants. The genes harboring more variants were HLA-A (4 variants) and ADAMTS7 (2) in cases; and PLIN4 (2) in controls (Table). We trained several ML models on the discovery cohort using as input the 16 significant individual variants and the number of variants in the 33 enriched genes. We tested them in the validation cohort obtaining accuracy of 72% and AUC-ROC of 87.4% with the best model (SVC), using 16 variants as input, confirming their association with the phenotypes. Functions of validated genes included oncogenes, tumor-suppressors, DNA repair, maintenance of genomic stability, HLA mediated antigen presentation and regulation of proliferation, migration, apoptosis and inflammatory pathways. Conclusions: Individuals presenting phenotypes of extreme high and low risk of developing tobacco-induced lung adenocarcinoma have different germline profiles. Our strategy may allow to identify high-risk subjects and to develop new therapeutic approaches. [Table: see text]
Utility of pharmacogenomic testing in predicting intolerance to BTK inhibitors.
Authors: Fahmin Basher, Micaela R Scobie, Michael J. Kelley, Deepak Voora, Daphne Ruth Friedman
Journal: Journal of Clinical Oncology (2023)

7541 Background: Oral inhibitors of Bruton’s tyrosine kinase (BTKi) are used for a number of B-cell malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma (LPL). Real-world data has demonstrated that BTKi discontinuation is commonly due to intolerance, but contributing factors are not fully understood. Prior work suggests that cytochrome P450 (CYP) polymorphisms may increase the risk of targeted therapy discontinuation in CLL. We utilized pharmacogenomic (PGx) testing in Veterans treated with BTKi to evaluate the potential contribution of CYP polymorphisms to intolerance and responses to BTKi. Methods: We identified Veterans receiving care through the Veterans Administration (VA) who were prescribed a BTKi and underwent testing through the Pharmacogenomic Testing for Veterans (PHASER) program, currently offered at 22 VA facilities. We analyzed factors including time on BTKi therapy, reasons for discontinuation, and use of concomitant medications known to strongly inhibit CYP. Event-free survival (EFS) was defined as time from BTKi initiation to discontinuation. Results: Eighty-nine Veterans treated with BTKi who had PGx testing were identified, of which 97% (86) were male and 85% (76) were diagnosed with CLL. Other diagnoses included LPL (4), MCL (3), and MZL (3). Seventy-seven patients (pts) were treated with ibrutinib, nine with acalabrutinib and three with zanubrutinib. Three pts had poor metabolizer genotype (PMG) for CYP2C19 and 25 pts received strong CYP2C19 inhibitors (inh). Thirty-two pts had PMG for CYP2D6, and 12 pts received strong CYP2D6 inh. With a median follow up time of 38.9 months, 25 pts (28%) permanently discontinued due to intolerance and 10 pts (11%) progressed on BTKi therapy. Another 25 pts temporarily discontinued therapy. Median duration of BTKi therapy was 11.0 months for pts discontinuing for intolerance, 23.2 months for pts discontinuing for progression, and 38.5 months for pts not discontinuing therapy. Reasons for intolerance included arrhythmia, bleeding, and infections. EFS due to intolerance or progression was not statistically different between pts who were either CYP2C19 PMG or who received strong CYP2C19 inh, compared to all other pts. Interestingly, EFS due to intolerance alone was statistically different comparing these groups (p = 0.014, median 49.4m vs NR), but EFS due to progression was not (p = 0.76, median 79.6m vs NR). EFS was not significantly different comparing pts who were either receiving strong CYP2D6 inh or were PM to those who were not. Conclusions: We found that Veterans who were treated with BTKi and who either took concomitant strong CYP2C19 inh or had a CYP2C19 PMG were more likely to have intolerable side effects of BTKi therapy leading to discontinuation. Our results suggest that evaluating polypharmacy and PGx factors should be considered when prescribing BTKi.
Association of single-click radiomic classifier with response and prognosis in non-small cell lung cancers (NSCLC) treated with immune checkpoint inhibitors.
Authors: Amogh Hiremath, Haojia Li, Allison Clement, Amit Gupta, Vamsidhar Velcheti, Anant Mababhushi, Nathaniel Braman
Journal: Journal of Clinical Oncology (2023)

8574 Background: Radiomics has shown promise to non-invasively phenotype disease and address the limitations of extant biomarkers (e.g. PD for immune checkpoint inhibitors (ICI) in cancers, such as NSCLC. However, considerable barriers to the clinical adoption of these tools remain, such as their dependence on precise annotation of tumor extent by experienced clinical users. Here, we demonstrate a radiomic solution that requires only a single user mouse click within one or more target lesions on a baseline CT scan, to contour tumors in 3D and generate a patient-level radiomic prediction of response and outcome in ICI treated NSCLC patients. Methods: 1778 CT scans from 1261 patients were used to develop and validate an interactive, semi-automated tool for predicting ICI outcomes in NSCLC patients prior to therapy. A user click based deep learning contouring model was trained and validated on 1146 patients, then used to create annotations for radiomic analysis. A least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model was utilized to select features associated with post-ICI overall survival (OS) and derive a radiomic risk score within a training cohort (n=74) that can separate patients into high and low risk groups. The model was tested on held out pre-treatment CTs of 41 ICI recipients from 2 institutions for association with OS, progression-free survival (PFS), and objective response (OR). Results: A total of 77 lesions were identified and segmented within the testing set. Average volume per lesion was 54.10 mL and per patient was 101.60 mL. OR was observed in 48.70% of patients. A threshold of -0.31 defining high and low radiomic risk groups was chosen based on optimal separation within the training set (HR=2.59 [95% 1.48~4.50], p=0.0009). Radiomic risk groups significantly stratified patients by OS (C-index=0.64, HR=3.03 [95% 1.15~8.02], p=0.03) and PFS (C-index=0.59, HR=3.20 [95% 1.13~9.10], p=0.03). Radiomic IO risk group was independently prognostic of clinical variables (Table 1) and further predicted ICI response with AUC=0.74 [95% 0.71-0.78]. Conclusions: From a single click in target lesions, our model was able to predict response and prognosis of ICI recipients from a baseline radiology scan. Additional multi-site validation and prospective evaluation will assess the value of the radiomics classifier as a decision support tool in the clinic. [Table: see text]
Real-world associations among patient-physician sex concordance, treatment practices, and cancer outcomes.
Authors: Philip Q. Ding, Dylan E. O'Sullivan, Rubab Shamsi, Aisha Wada, Christie Farrer, Colleen Ann Cuthbert, Darren R Brenner, Winson Y. Cheung
Journal: Journal of Clinical Oncology (2023)

e18511 Background: Prior research has linked patient-physician sex discordance with inferior surgical and cardiac outcomes. The impact of such sex inequities may be magnified in medical oncology, where patients often face a life-limiting illness and physicians assume the role of primary healthcare provider. This study examined cancer treatment practices and survival outcomes in sex-concordant vs. discordant patient-physician dyads. Methods: This was a population-based, retrospective cohort study of adults diagnosed with stage II-IV colon or lung cancer in 2013-2020 in Alberta, Canada and referred to a medical oncologist. Study data included physician- and patient-level demographics and cancer disease characteristics. Patient-physician dyads were classified as sex-concordant (female-female, male-male) or discordant (female-male, male-female). Time-to-event data were analysed using Kaplan-Meier methods and associations were assessed with Cox and logistic regression. Results: A total of 11,131 patients and 188 medical oncologists were included. Among patients, 49% were female and 50% were in sex-concordant patient-physician dyads. The median age was 68 years, 7615 (68%) had lung cancer, and 6016 (54%) had stage IV disease. In sex-concordant and discordant dyads, respectively, median overall survival (OS) was 17.1 and 18.7 months ( p = 0.047) while median cancer-specific survival (CSS) was 20.2 and 22.4 months ( p = 0.21). In multivariable analysis, sex-concordance was not significantly associated with OS or CSS in the overall cohort and in female patients. However, among male patients, sex-discordance was significantly associated with lower OS (hazard ratio [HR], 1.11; 95% CI, 1.04-1.19) and CSS (HR, 1.12; 95% CI 1.04 -1.21), largely driven by differences in survival outcomes in stage IV disease. Older age, higher comorbidity burden, lung cancer, and advanced stage correlated with worse outcomes in all multivariable models. Sex concordance was not significantly associated with adjuvant systemic anti-cancer therapy (SACT) use in stage II-III disease or with SACT use in stage IV disease. Treatment practices are summarized in the table. Conclusions: Sex concordance between patients and medical oncologists did not generally correlate with differential SACT use and survival. However, male patients treated by female physicians had worse outcomes compared to those treated by male physicians. Cancer outcomes may be prone to the effects of sex bias in specific patient-physician relationships. [Table: see text]
Just ASK: A quality improvement project to enhance smoking assessment and treatment.
Authors: Graham W. Warren, Jamie S. Ostroff, Timothy Mullett, Robert Adsit, Jessica Burris, Audrey Darville, Michael C. Fiore, Ellen Hahn, Laurie Kirstein, Danielle McCarthy, Heidi Nelson, Eileen Reilly, Rachel C Shelton, Elisa Tong
Journal: Journal of Clinical Oncology (2023)

6571 Background: Persistent smoking after cancer diagnosis causes adverse clinical outcomes. ASCO and other organizations view smoking assessment and treatment as indicators of high-quality cancer care. Yet, adoption of clinical practice guidelines like the 3As (Ask, Advise and Assist) for smoking assessment and treatment has been slow and inconsistent in cancer care settings. Methods: Led by the American College of Surgeons Cancer Programs’ Commission on Cancer (CoC) and National Accreditation Program for Breast Centers (NAPBC), the “Just ASK” national quality improvement project focuses on enhancing smoking assessment and treatment in cancer care settings. All CoC/NAPBC programs (n~2000) were invited to participate, which consisted of educational webinars, online resources, and 3 online surveys (baseline, 6- and 12-month) collecting information on smoking assessment and treatment practices, plus other variables (e.g., organizational priority, implementation barriers). Program participation was incentivized by fulfillment of accreditation standards. Results: In total, 776 programs (731 CoC, 45 NAPBC), participated. At baseline, most programs strongly endorsed the importance of addressing smoking within cancer care and the majority of programs reported routinely assessing smoking (90%) and advising all patients reporting current smoking to quit (71%). However, routine delivery of evidence-based smoking cessation assistance (e.g., quitline referral, cessation medications, counseling services) was low (all &lt; 30%). Program retention was excellent (91%). As shown in the table, the 12-month follow-up revealed marked improvements in evidence-based Ask, Advise and Assist, practices. Conclusions: At enrollment, the importance of addressing smoking was evident and high rates of smoking assessment were reported. At 12-month follow-up, marked improvement was reported in all quality indicators of the 3As. These findings guided the sharing of strategies for improving patient assessment, clinical workflow and documentation. Suboptimal delivery of smoking cessation assistance persisted despite overall improvements, which highlight persistent challenges and opportunities for implementing smoking assessment and treatment in cancer care settings. [Table: see text]
A retrospective analysis of the outcomes among hospitalized patients with myeloid leukemia undergoing leukapheresis: Insight from the National Inpatient Sample.
Authors: Yajur Arya, Arshi Syal, Bruce Adrian Casipit, Claudia Dourado
Journal: Journal of Clinical Oncology (2023)

e19021 Background: Hyperleukocytosis often complicates the clinical picture in hematological malignancies. Historically, leukapheresis has been used to reduce the quantity of circulating white cells to reduce leukostasis, which can predispose to hypercoagulability and thromboembolism. Literature shows that leukapheresis does not offer any long-term survival benefits to patients, with some evidence of even worse outcomes at 6 months. Methods: We utilized the 2018-2020 National Inpatient Sample (NIS) Database in conducting a retrospective cohort study. We identified hospitalized patients who have myeloid leukemia undergoing leukapheresis using appropriate ICD-10 CM codes. We stratified patients based on whether they underwent leukapheresis or not. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of &lt; 0.05 was considered statistically significant. The aim of this study is to investigate the outcomes among hospitalized patients with myeloid leukemia undergoing leukapheresis looking primarily at the in-hospital mortality, hospital length of stay (LOS) as well as total hospital charges. Results: We identified a total of 27,000 hospitalized patients with acute and chronic myeloid leukemia, of which 0.5% (135/27,000) underwent leukapheresis. The overall in-hospital mortality among those with myeloid leukemia was 9.86% (2662/27,000). Among those who underwent leukapheresis, the overall in-hospital mortality rate was significantly higher at 22.22% (30/135) (p = 0.05). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, the use of leukapheresis among hospitalized myeloid leukemia patients did not significantly decrease the risk for in-hospital mortality (adjusted OR 2.54 95% confidence interval [CI], 0.84-7.73; p = 0.10), hospital LOS (adjusted OR 2.76; 95% confidence interval [CI], -2.11-7.62; p = 0.27) or total hospital charges (p = 0.19). Conclusions: Our analysis showed that among hospitalized patients with myeloid leukemia, leukapheresis did not significantly decrease the risk for in-hospital mortality, hospital LOS as well as total hospital charges. Caution should be exercised in interpreting the higher rate of in-hospital mortality among those who underwent leukapheresis as the higher mortality rate can be due to small sample size, or the fact that patients who require leukapheresis have uncontrolled and more advanced disease. Hyperleukocytosis in these patients may indicate a worse prognosis. A prospective study with a larger sample size to test for possible confounders is warranted in order to further delineate these associations.
Web-based patient educational material on chimeric antigen receptor T-cell therapy: Quantitative assessment of readability.
Authors: Rahul Kumar Thakur, Anurag Adhikari, Karun Neupane, M Bakri Bakri Hammami, Charan Thej Reddy Vegivinti, Rama Al Hamed, Eleftheria Atalla, Sindhu Vikash, Ansh Mehta, Abhishek Kumar
Journal: Journal of Clinical Oncology (2023)

11040 Background: Chimeric antigen receptor (CAR) T-cell therapy is another paradigm-shifting advancement for hematologic malignancies, creating unprecedented treatment options. However, there is still a lack of knowledge and understanding among patients regarding this novel therapy. Most patients turn to online resources, ranging from social media to federal websites, to gather health information to supplement decision-making. Given that the average American adult reads between the sixth- and eighth-grade levels, national organizations recommend that patient resources be written at the sixth-grade level or below. The purpose of this study was to evaluate web-based patient educational material on CAR -T cell therapy resources using measures of readability and compare it to national guidelines. Methods: Online patient information on CAR-T cell therapy from the top 20 U.S Cancer center as per US news ranking was collected. We analyzed the content by six of the most common readability tests- Flesch Reading Ease score (FRE), Gunning Fog (GF), Flesch-Kincaid Grade Level (FKGL), Coleman-Liau Index (CLI), Simple Measure of Gobbledygook (SMOG) Index, and the Automated Readability Index (ARI). The text from each article was carefully reviewed and analyzed using the software Readable, and the readability scores with standard deviation (SD) were obtained. Results: The mean score FRE score was 48.5 (SD: 6.7), which corresponds to college level and is difficult to read. The mean GF score was 8.7(SD: 1.5), which represents the writing of an 8th grader. The FKGL score was 8.6 (SD: 1.1), which represents a level of 8th grade or above. The mean CLI score was 11.5(SD: 1.3), which is the text level for high school juniors. The mean SMOG index was 10.9 (SD: 1), which is the level of a 12th grader. The ARI score was 7.8 (SD: 1.3), indicating a 7th-grade level. Conclusions: Overall, web-based CAR- T cell therapy patient educational materials scored poorly and does not meet the national recommendations. Authors of patient resources should incorporate readability criteria and prompt a revision or creation of new educational materials including videos and audio to support general patient understanding. By making CAR-T therapy information easily understandable, internet users can be better informed about their treatment decisions.
Reduced blood product utilization via implementation of an anemia clinic and consult service in a large health system hospital.
Authors: Reid Christian Bowers, Sandra Tomany Korman, Michael A. Thompson, Sherjeel Sana, Manish Krishna Pant, Federico Augusto Sanchez
Journal: Journal of Clinical Oncology (2023)

e18716 Background: An Anemia Clinic program was started Sept. 2016 as part of system wide implementation of Patient Blood Management (PBM) initiated in 2015. Methods: The Anemia Clinic accepted referrals for non-cancer anemia, predominantly preoperative cardiovascular surgery (CVS) Pts. Hgb thresholds were &lt; 13 g/dL in men and &lt; 12 g/dL in women. Non-anemia cytopenias triggered Hematology referral. All Pts were screened for iron, B12, folate, and reticulocyte count. Nutrient deficiencies were supplemented. Pts with CKD or chronic disease were considered for erythropoiesis stimulating agents. Results: PBM implementation resulted in a drop in packed red blood cell (PRBC) usage (Table). Of CVS Pts pre-operatively anemic in 2022, 211 were referred to the Anemia Clinic and 373 were not. The percentage of Pts who received PRBCs after Anemia Clinic referral was not statistically different from those who were not referred (61.1% vs. 54.2% chi-square p = 0.10). Of preoperatively anemic Pts who were transfused in 2022, an average of 2.41 PRBCs were used in the referred group vs. an average of 2.21 PRBCs in those in the not referred group (negative binomial p = 0.25). Length of stay (LOS) which was a median 10d ( P 25 = 6d, P 75 = 17d) in the referred group vs a median 10d ( P 25 = 7d, P 75 = 17d) in the non-referred group was not statistically different between groups (Kolmogorov-Smirnov p = 0.84). LOS analyses of observed-to-expected (O/E) ratios used the Premier Healthcare Providers Alliance Database (PHD) which contains data on approximately 45% of US hospital discharges. For 2022 through Nov. the referred group had an O/E = 0.93 (observed LOS μ geo = 10.51 days, expected LOS μ geo = 11.32 days, N = 183). The not referred group had an O/E = 1.10 (observed LOS μ geo = 10.44 days, expected LOS μ geo = 9.50 days, N = 321). Conclusions: PBM decreased PRBC use through systematization of best practices during the initial year, and that decrease has persisted for seven years. Subsequent addition of Anemia Clinic services did not decrease PRBC use further. A trend toward shorter LOS for patients referred to Anemia Clinic was not observed this year, but the difference in LOS from the not referred group is not statistically significant and observed LOS for the referred group was lower than expected LOS. Our methods improved nutrient deficiency identification which may improve both later health outcomes not detected here and access to treatment for hematologic malignancies. [Table: see text]